HPV Vaccines: Progress to date and future worldwide directions – Abstract #19
Douglas R. Lowy presented on current effects of HPV vaccination and future directions for second generation vaccines. Interestingly, the current HPV vaccine has unprecedented immunogenicity for a protein based sub-unit vaccine. Even with one dose, persistence of antibodies to HPV 16 lasts for around four years. However, the antibody effect is orders of magnitude lower than if 2 or 3 vaccines are given.
Administration of two vaccine doses has just been licensed in Europe for the bivalent (Cervarix) vaccine and approval is expected soon for the quadrivalent Gardasil.
Second generation vaccines are expected to provide broader protection and/or be less expensive. Examples of possibilities are simplified administration regimens (e.g. add HPV 16 L1 to measles vaccine) or broader protection against more serotypes.
Merck is currently trialling a 9-valent vaccine with the 5 next most oncogenic HPV subtypes 45, 31, 33, 52, 58. So far results look promising.
Currently, HPV vaccines are against L1 proteins, which are serotype specific. Future possibilities are for vaccines against HPV L2 proteins, which contain cryptic cross-neutralisation epitopes. If a successful vaccine was created, then there is the potential for a pan-HPV vaccine. However, no vaccine has ever been developed against cryptic epitopes.
This series of presentations demonstrated the role for early ART in infants. Where there is early treatment, infants become seronegative. Use of antibody status should not be used for diagnosis of HIV if ART started before 6 months of age. Where there is older ART initiation, infants show higher anti-gp120 IgG, which is associated with higher cumulative viral loads.
The age of ART initiation influences the degree of viral suppression and virologic control after viral suppression (better results where initiation is before 6 months of age).
Early viral suppression also correlates to better neurocognitive outcomes in HIV infected children with better testing scores (WISC III and IV), which becomes statistically significant around age 4-5 years.
An interesting point raised that the lack of antibodies in early treated infants reflects a lack of inflammation or immune activation. This may represent a functional cure, and may lead to better clinical outcomes.